The scientific and commercial objective of the proposed research is to improve the medical prevention of kidney stones in children by developing new clinical assays that can predict the development of stones in children with nephrolithiasis and the syndrome of hematuria due to hypercalciuria. Currently available technology, consisting of routine urine chemistry measurements, is a poor predictor of a patient's risk for developing stones. Early diagnosis and treatment of stones, or conditions such as hypercalciuria that predispose children to stones, is important because of the high life-long risk of recurrence and potential morbidity of the disease. We have found three proteins that are known inhibitors of calcium oxalate crystal growth to be significantly altered in the urine of adult stone formers. Preliminary studies of adult family members of calcium stone formers have shown that measurements of these proteins vastly improved the discrimination of stone formers from non stone formers compared to standard urine chemistries alone. Our hypothesis is that alterations in these proteins in the urine of kidney stone patients may serve as markers of stone disease activity or vulnerability to recurrence. Children have a lower prevalence of nephrolithiasis than adults, and urine from children has a greater ability to inhibit crystallization than that of adults. We propose to investigate whether variations in urine crystallization properties or in specific inhibitor proteins are associated with stone disease in children as they are in adults. Likewise, we plan to examine whether variations in any of these factors are linked with hematuria due to hypercalciuria. We wish to identify the assay(s) that best discriminate non stone forming children from those with stones or hypercalciuria with hematuria, and to ask whether they can be used along with or instead of conventional risk factors to improve the management of these disease states.